The overall objective of this project is to define interactions between endogenous vasoactive peptides and specific target cells in the lung. The major emphasis is on how these interrelations are involved in normal cell function and in injury or inflammation. Cells cultured from pulmonary blood vessels are the focus of these studies. Endothelial cells, smooth muscle cells and fibroblasts are used to determine how peptides can stimulate normal cell functions (growth in culture, release of enzymes, formation of prostaglandins). The interactions of peptides such as angiotensin, bradykinin, complement peptide C3a and C5a, vasoactive intestinal peptide, substance P, with specific receptors will be investigated. The stimulation of specific cell receptors and changes in cell functions will be correlated. Further, the influence of enzymes within the particular cells that metabolize vasoactive peptides will be investigated. For example, endothelial cells contain an enzyme that activates angiotensin (angiotensin I converting enzyme; or kininase II) and an enzyme that inactivates it (angiotensinase A). It is important to understand how these enzymes may be interrelated on the cell membrane or on structures within the cells. Other cell types, such as smooth muscle cells and fibroblasts, also contain enzymes that metabolize angiotensin and kinins. Definition of the particular peptides that are metabolized by these cells, and the localization of the enzymes within the cells are facets of this overall study.